For about a decade, scientists have been able to transform mature cells into stem cells.
The process involves inserting a handful of genes into the nucleus of an already differentiated cell, like a skin cell. These genes tell the cell to revert back to a primordial, undifferentiated state like those found in early embryos.
Such cells are called “induced pluripotent stem cells,” or iPS cells, and their ability to turn into any cell in the human body means they have huge scientific and therapeutic potential.
But the laboratory technique scientists currently use to make iPS cells takes a long time and doesn’t produce a lot of cells. That’s a big stumbling block for research.
This month, a group of Swiss researchers announced they may have found a way to speed things up and allow them to ditch the Petri dish.
“What we currently have available is this two dimensional plastic surface that many, many stem cells really don’t like at all,” said Matthias Lutolf, Ph.D., professor at Ecole Polytechnique Federale de Lausanne in Switzerland and senior author of the study, which was published in the journal Nature Materials.
Going 3-D For Better Growth
Lutolf told Healthline that he and his team hypothesized that the pluripotent cells would behave differently if they were in an environment that better mimicked the three-dimensional conditions of the human body.
In the body, cells are suspended in a network of collagen and other molecules known as the extracellular matrix. The team could more or less approximate this environment with a human-made polymer known as a PEG (polyethylene glycol) gel.
What they found was that both mouse and human cells grown in the gel transformed into iPS cells more efficiently and more quickly than cells cultured in a Petri dish. In fact, the gel cells transformed in half the time it took cells grown in a dish.
Their innovation could be a real boon for stem cell scientists, said Kevin Whittlesey, a senior science officer at the California Institute for Regenerative Medicine.
Currently, it take months to grow iPS cells in the laboratory and months beyond that to produce the specific cells a scientist might want in the quantity needed for research, he said. And that means paying for lots of expensive lab equipment.
“In any of these manufacturing processes, time is money,” Whittlesey told Healthline.
If the process could be scaled up the payoff is potentially huge — and not just financially.
Theoretically, scientists of the future could take cells from a patient’s skin, turn them into stem cells, and then grow any tissue that the patient needs. This would result in organ transplants that are a perfect match between donor and recipient — because they are the same person.
“We’re talking about cures, not treatments,” Whittlesey said.
Both embryonic and iPS cells could also be used to study diseases at the cellular level and to screen drugs for side effects in the lab before administering them to patients.
Problems That Need Fixes
But there are still plenty of barriers separating patients from stem cell cures.
By definition, stem cells divide unchecked, just like cancer cells. Introducing undifferentiated stem cells into a patient would put the patient at risk for cancer.
Also, both embryonic and iPS stem cells are notoriously hard to control. Even cells lines derived from the same parent cell — which should be genetically identical — can behave differently than one another. Some cell lineages are much better than others at becoming certain tissues. No one really understands why.
The gel experiment doesn’t address either of these problems. Lutolf explains that his team merely showed “proof of principle” that the gel can be used successfully to manufacture stem cells, although they’re not exactly sure why it works so well.
He suspects it has to do with the way the cells are shaped as they grow.
“In using a three-dimensional environment, we sort of force cells mechanically to grow like stem cells,” Lutolf said.
Round is Better Than Flat
The skin cells from which the iPS cells are derived are much flatter than stem cells. The broad plane of a Petri dish encourages the cells to spread out like their parent skin cells.
But in the gel matrix, the impressionable young cells are confined on all sides, creating an environment much better suited to round stem cells than flat skin cells.
This is not the first time cells have been cultured in 3-D environments. In fact, scientists have grown miniature organs by allowing stem cells to self-organize in gel matrices. A Dutch lab grew a miniature mouse gut this way in 2009.
That discovery has inspired Lutolf to turn next to the investigation of such miniature organs, also known as “organoids.”
“We think this is really going to change the way people discover drugs and test drugs,” he said.
And maybe, some day, treat patients.